DESCRIPTION: A stable transformed fibrosarcoma cell line has been derived containing the C/EBP-alpha gene under control of the lac repressor. Preliminary studies have demonstrated that C/EBP-alpha expression leads to growth arrest and increased expression of p21/WAF1/SDI1. The latter is an important negative regulator of cell proliferation. Also, co-immunoprecipitation has demonstrated direct binding of C/EBP-alpha to p21. In Aim I, a two hybrid expression system will be used to determine whether this binding occurs in vivo. Then, to further define cellular pathways that regulate interaction of the two proteins, a subtraction cDNA library will be constructed, enriched for genes differentially activated by C/EBP-alpha. This library will be the source of genes that can be tested for their ability to alter p21 expression. In Aim II, liver regeneration will be studied in the p21 knock-out mouse. Finally, Aim III studies will investigate liver regeneration in old rats, which have altered regulation of both C/EBP-alpha and p21.